The role of resistance exercise training & IGF-1 signaling in the amelioration of mild cognitive impairment in female Wistar rats

Mild cognitive impairment increases risk for dementia. One therapeutic intervention that is reported to ameliorate cognition in patients with mild cognitive impairment is resistance exercise. However, the underlying neuro-molecular mechanisms behind resistance exercise are largely unknown. To better understand the underlying neuro-molecular mechanisms, I established a preclinical model of resistance-exercise training and mild cognitive impairment based off the literature. Ladder climbing in female Wistar rats let to similar increases in muscle mass and strength as those observed in humans, while intracerebroventricular injections of lipopolysaccharides (LPS) induced neuroinflammation and cognitive deficits, which resembled clinical mild cognitive impairment. Resistance-exercise training restored cognitive function, increased IGF-1R phosphorylation and subsequent downstream signaling, and ameliorated neuroinflammation. Selective IGF-1R inhibition in the dentate gyrus, with picropodophyllin, had differential effects on cognition dependent on training status and type of cognition measured. Collectively, these studies indicate that although resistance training and IGF-1 signaling both ameliorate LPS-induced neuroinflammation, IGF-1 signaling during resistance-exercise training, but is only necessary for its ability to ameliorate mild cognitive impairment after a single workout. Furthermore, we made a novel discovery where dentate gyrus IGF-1R inhibition can improve specific forms of cognition. These findings reveal the complexity of IGF-1 signaling and open new areas of study that could offer insights for the treatment of mild cognitive impairment.Includes bibliographical references (pages 126-156)